Skip to main content
construction release_alert
The Scholars Team is working with OIT to resolve some issues with the Scholars search index
cancel
Journal cover image

BMP antagonism by Noggin is required in presumptive notochord cells for mammalian foregut morphogenesis.

Publication ,  Journal Article
Fausett, SR; Brunet, LJ; Klingensmith, J
Published in: Dev Biol
July 1, 2014

Esophageal atresia with tracheoesophageal fistula (EA/TEF) is a serious human birth defect, in which the esophagus ends before reaching the stomach, and is aberrantly connected with the trachea. Several mouse models of EA/TEF have recently demonstrated that proper dorsal/ventral (D/V) patterning of the primitive anterior foregut endoderm is essential for correct compartmentalization of the trachea and esophagus. Here we elucidate the pathogenic mechanisms underlying the EA/TEF that occurs in mice lacking the BMP antagonist Noggin, which display correct dorsal/ventral patterning. To clarify the mechanism of this malformation, we use spatiotemporal manipulation of Noggin and BMP receptor 1A conditional alleles during foregut development. Surprisingly, we find that the expression of Noggin in the compartmentalizing endoderm is not required to generate distinct tracheal and esophageal tubes. Instead, we show that Noggin and BMP signaling attenuation are required in the early notochord to correctly resolve notochord cells from the dorsal foregut endoderm, which in turn, appears to be a prerequisite for foregut compartmentalization. Collectively, our findings support an emerging model for a mechanism underlying EA/TEF in which impaired notochord resolution from the early endoderm causes the foregut to be hypo-cellular just prior to the critical period of compartmentalization. Our further characterizations suggest that Noggin may regulate a cell rearrangement process that involves reciprocal E-cadherin and Zeb1 expression in the resolving notochord cells.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Dev Biol

DOI

EISSN

1095-564X

Publication Date

July 1, 2014

Volume

391

Issue

1

Start / End Page

111 / 124

Location

United States

Related Subject Headings

  • Trachea
  • Time Factors
  • Phenotype
  • Notochord
  • Mutation
  • Mice, Transgenic
  • Mice
  • In Situ Hybridization
  • Hedgehog Proteins
  • Genotype
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Fausett, S. R., Brunet, L. J., & Klingensmith, J. (2014). BMP antagonism by Noggin is required in presumptive notochord cells for mammalian foregut morphogenesis. Dev Biol, 391(1), 111–124. https://doi.org/10.1016/j.ydbio.2014.02.008
Fausett, Sarah R., Lisa J. Brunet, and John Klingensmith. “BMP antagonism by Noggin is required in presumptive notochord cells for mammalian foregut morphogenesis.Dev Biol 391, no. 1 (July 1, 2014): 111–24. https://doi.org/10.1016/j.ydbio.2014.02.008.
Fausett SR, Brunet LJ, Klingensmith J. BMP antagonism by Noggin is required in presumptive notochord cells for mammalian foregut morphogenesis. Dev Biol. 2014 Jul 1;391(1):111–24.
Fausett, Sarah R., et al. “BMP antagonism by Noggin is required in presumptive notochord cells for mammalian foregut morphogenesis.Dev Biol, vol. 391, no. 1, July 2014, pp. 111–24. Pubmed, doi:10.1016/j.ydbio.2014.02.008.
Fausett SR, Brunet LJ, Klingensmith J. BMP antagonism by Noggin is required in presumptive notochord cells for mammalian foregut morphogenesis. Dev Biol. 2014 Jul 1;391(1):111–124.
Journal cover image

Published In

Dev Biol

DOI

EISSN

1095-564X

Publication Date

July 1, 2014

Volume

391

Issue

1

Start / End Page

111 / 124

Location

United States

Related Subject Headings

  • Trachea
  • Time Factors
  • Phenotype
  • Notochord
  • Mutation
  • Mice, Transgenic
  • Mice
  • In Situ Hybridization
  • Hedgehog Proteins
  • Genotype